PMID- 37587291
OWN - NLM
STAT- MEDLINE
DCOM- 20240103
LR  - 20240106
IS  - 2190-3948 (Electronic)
IS  - 2190-393X (Linking)
VI  - 14
IP  - 2
DP  - 2024 Feb
TI  - Modulation of microglial polarization by sequential targeting surface-engineered 
      exosomes improves therapy for ischemic stroke.
PG  - 418-432
LID - 10.1007/s13346-023-01408-6 [doi]
AB  - Microglia are important cells that act on regulating neuroinflammation and 
      neurofunction after the induction of ischemic stroke (IS). Consequently, the 
      efficient accumulation of drugs within ischemic regions, particularly in 
      microglia, serves as a valuable approach for achieving effective therapy by 
      attenuating microglia-mediated cerebral ischemic injury. In this study, we 
      designed mannose (man)-conjugated luteolin (lut)-loaded platelet-derived exosomes 
      (lut/man-pEXO) as surface engineered multifunctional cascade-delivery drug 
      carriers to target ischemic blood vessels and subsequent microglia to enhance 
      drug accumulation and induce neuroprotection of neurovascular unit (NVU) against 
      IS. The results revealed that as platelets naturally gathered in pathological 
      ischemic cerebral vessels, lut/man-pEXO could bind to platelets and efficiently 
      target ischemic injury sites. Moreover, owing to the selective binding affinity 
      of mannose present in lut/man-pEXO towards the mannose receptor expressed on 
      microglia, lut/man-pEXO exhibited superior microglia-targeting properties, 
      inducing the increased uptake of lut by microglia. As a result, lut/man-pEXO 
      regulated microglia by inhibiting the activation of detrimental M1 and promoting 
      the transition towards the anti-inflammatory type (M2), thus attenuating ischemic 
      damage of NVU by reducing the infarct area, rescuing the damage of blood-brain 
      barrier (BBB) and preventing inflammatory transformation of astrocytes.
CI  - (c) 2023. Controlled Release Society.
FAU - Liu, Xintong
AU  - Liu X
AD  - School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People's 
      Republic of China.
FAU - Hao, Yunni
AU  - Hao Y
AD  - School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People's 
      Republic of China.
FAU - Huang, Zhixuan
AU  - Huang Z
AD  - School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People's 
      Republic of China.
FAU - Shi, Yijie
AU  - Shi Y
AD  - School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People's 
      Republic of China.
FAU - Su, Chang
AU  - Su C
AD  - School of Veterinary Medicine, Jinzhou Medical University, Jinzhou, 121000, 
      People's Republic of China.
FAU - Zhao, Liang
AU  - Zhao L
AUID- ORCID: 0000-0002-3464-6956
AD  - School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People's 
      Republic of China. liangzhao79@163.com.
LA  - eng
GR  - JYTJCZR2020067/Project of Liaoning Educational Committee/
GR  - JYTQN2020015/Project of Liaoning Educational Committee/
PT  - Journal Article
DEP - 20230816
PL  - United States
TA  - Drug Deliv Transl Res
JT  - Drug delivery and translational research
JID - 101540061
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Humans
MH  - Microglia/metabolism/pathology
MH  - *Stroke/drug therapy/metabolism/pathology
MH  - *Ischemic Stroke/metabolism/pathology
MH  - *Brain Ischemia/drug therapy/metabolism/pathology
MH  - *Exosomes/metabolism/pathology
MH  - Mannose
OTO - NOTNLM
OT  - Luteolin
OT  - Mannose
OT  - Microglia
OT  - Platelet-derived exosomes
EDAT- 2023/08/17 00:42
MHDA- 2024/01/03 09:44
CRDT- 2023/08/16 23:30
PHST- 2023/08/01 00:00 [accepted]
PHST- 2024/01/03 09:44 [medline]
PHST- 2023/08/17 00:42 [pubmed]
PHST- 2023/08/16 23:30 [entrez]
AID - 10.1007/s13346-023-01408-6 [pii]
AID - 10.1007/s13346-023-01408-6 [doi]
PST - ppublish
SO  - Drug Deliv Transl Res. 2024 Feb;14(2):418-432. doi: 10.1007/s13346-023-01408-6. 
      Epub 2023 Aug 16.